Use of an Extract of Annona muricata Linn to Prevent High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice.
ABSTRACT: Annona muricata Linn, commonly known as graviola, is one of the most popular plants used in Brazil for weight loss. The aim of this study is to evaluate the therapeutic effects of three different doses (50 mg/kg, 100 mg/kg, and 150 mg/kg) of aqueous graviola leaf extract (AGE) supplemented by oral gavage, on obese C57BL/6 mice. Food intake, body weight, an oral glucose tolerance test (OGTT), an insulin sensitivity test, quantification of adipose tissue cytokines, weight of fat pads, and serum biochemical and histological analyses of the liver, pancreas, and epididymal adipose tissue were measured. AGE had an anti-inflammatory effect by increasing IL-10 at doses of 50 and 100 mg/kg. Regarding the cholesterol profile, there was a significant decrease in LDL-cholesterol levels in the AGE 150 group, and VLDL-cholesterol and triglycerides in the AGE 100 and 150 groups. There was an increase in HDL cholesterol in the AGE 150 group. The extract was able to reduce the adipocyte area of the epididymal adipose tissue in the AGE 100 and 150 groups. According to the histological analysis of the liver and pancreas, no significant difference was found among the groups. There were no significant effects of AGE on OGTT and serum fasting glucose concentration. However, the extract was effective in improving glucose tolerance in the AGE 150 group.
Project description:The anti-diabetic effects of Brazilian propolis were examined using ob/ob mice. Although repeated injection of an ethanol extract of Brazilian propolis (100 mg/kg, ip, twice a week for 12 weeks) did not affect body weight gain and food intake of ob/ob mice, blood glucose and plasma cholesterol levels were significantly attenuated. Moreover, the propolis extract partially restored glucose tolerance and insulin resistance, indicating anti-diabetic properties of the extract. The propolis-treated mice exhibited lower weight gain in mesenteric adipose tissue, while weight gains in inguinal and epididymal adipose tissues were not modulated. Flow cytometric and microscopic analyses suggested that the extract promoted accumulation of eosinophils into mesenteric and epididymal adipose tissues. Alternatively, the ratio of M1-like macrophages to M2-like macrophages in mesenteric adipose tissue was reduced by the propolis injection, coincident with the decrement of the number of interleukin-12A(+) cells. Levels of M1 macrophage markers, such as Itgax and Il12b transcripts, were decreased in the vascular stromal fraction of mesenteric adipose tissue, whereas those of pan-macrophage markers Emr1 and Cd68 were not influenced. Microarray and subsequent gene ontology term analyses suggested that propolis attenuated immune activation in mesenteric adipose tissues. Taken together, this indicates that Brazilian propolis improves diabetes in ob/ob mice, presumably through modification of immune cells in mesenteric adipose tissues.
Project description:The effects of a mixture of Hippophae rhamnoides (HR) and Zingiber mioga (ZM) extract (ZH) on intracellular lipid accumulation were investigated in vitro and the anti-obesity effects of ZH evaluated in mice with high-fat diet-induced obesity. The results revealed that ZH inhibited lipid accumulation in 3T3-L1 adipocytes and Huh-7 cells by suppressing adipogenic and lipogenic gene and protein expression. To evaluate the anti-obesity effects of ZH, mice fed a high-fat diet were orally administered low and high doses of ZH (low, ZM 400 mg/kg + HR 100 mg/kg; high, ZM 800 mg/kg + HR 200 mg/kg) for 9 weeks. ZH significantly reduced body weight gain and adipose tissue accumulation with no reduction in food intake when compared to control treatment. Furthermore, ZH reduced hepatic triglyceride and total cholesterol levels, as well as adipose cell size, in the liver and epididymal fat pads, respectively, through inhibition of adipogenesis and lipogenesis-related gene expression. These results suggested that ZH inhibits lipid accumulation, thereby indicating its potential for use as a new therapeutic strategy for obesity.
Project description:Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The purpose of this study was to investigate the antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in high fat diet-induced obese rats.Four week-old male Sprague-Dawley rats were randomly divided into four groups with 8 rats in each group for a period of 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf hot water extract, HFL group; high fat diet + lotus leaf hot water extract + taurine, HFLT group). Lotus leaf hot water extract was orally administrated to HFL and HFLT groups and the same amount of distilled water was orally administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v).The body weight gain and relative weights of epididymal and retroperitoneal adipose tissues were significantly lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed lower concentrations of total cholesterol, triglyceride and low density lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT group showed better blood lipid profiles compared to HFL group.Lotus leaf hot water extract with taurine supplementation showed antiobesity and hypolipidemic effects in high fat diet-induced obese rats, which was more effective than lotus leaf hot water extract alone.
Project description:The use of cyclophosphamide in cancer therapy is usually associated with challenging immunosuppression which exposes patients to increased risk of anemia and necessitating preventive measures during therapy. This study was carried out to investigate the efficacy of the hydro-ethanolic extract of the root of Z. zanthoxyloides in preventing and/or improving cyclophosphamide induced myelosuppression and oxidative stress in rats.Animals were divided into 6 groups of 6 rats each and were pretreated oral doses of 75, 150 and 225 mg/kg of the extract for 7 days and then co-administered with 2.5 mg/kg cyclophosphamide for 28 days.The LD50 of the extract was found to be 1682.3 mg/kg. Phytochemical analysis of the plant extract showed the presence of tannins, saponins, alkaloids and flavonoids, glycosides, terpenoids and phenols. In the anti-oxidant enzyme assay, CAT was significantly (p < 0.05) increased for animals treated with 150 mg/kg+CP compared to 75 mg/kg+CP and 225 mg/kg+CP. GPx was significantly (p < 0.01) increased in rats treated with 75 mg/kg+CP compared to 150 mg/kg+CP and control. SOD was significantly (p < 0.01) increased in rats treated with 75 mg/kg+CP compared to the control. WBC was significantly (p < 0.05) reduced for 225 mg/kg, 225 mg/kg+CP (p < 0.001), 150 mg/kg+CP (p < 0.001), 75 mg/kg+CP (p < 0.001) and CP administered rats (p < 0.001) respectively compared to the control. LDL and CHOL were significantly reduced (p < 0.05) for rats treated with 75 mg/kg+CP, 225 mg/kg+CP and 225 mg/kg.Findings from this study demonstrates that the hydro-ethanolic root extract of Z. zanthoxyloides could be beneficial in hyperlipidemia and in cases of malignancies with abnormal cholesterol metabolism an effect which may be mediated via combating oxidative stress. List of Abbreviations: EDTA: Ethylenediamine-tetra acetate; MDA: Malondialdehyde; PCV: Packed cell volume; RBC: Red blood cell; HGB: Hemoglobin; WBC: White blood cell; ALT: Alanine transaminase; AST: Aspartate transaminase; CHOL: Cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; GSH: Reduced glutathione; SOD: Superoxide dismutase; CAT: Catalase; CP: Cyclophosphamide.
Project description:In traditional oriental medicine, A. fistulosum and V. mandshurica are considered to be effective in promoting blood circulation. Therefore, in this study, we investigated whether a solution containing both A. fistulosum and V. mandshurica (AFE?+?VME) extracts has synergistic effects on the treatment of hyperlipidemia and obesity.Anti-obesity effects of an herbal extract containing Allium fistulosum and Viola mandshurica (AFE?+?VME) were investigated in high-fat diet (HFD)-induced obese mice. AFE?+?VME was orally administrated to mice with the HFD at a dose of 200 mg/kg/day for 8 weeks. We observed the effects of mixed extract on body weight, fat mass, serum lipid levels, and mRNA expression levels of lipid metabolism-related genes in the adipose tissue of mice.The nutritional analysis revealed that this mixed extract is high in carbohydrate (72.2 g/100 g) and protein (11.5 g/100 g); low in fat (1.7 g/100 g); rich in vitamins E (4.8 mg/100 g), B1 (14.8 mg/100 g), B2 (1.0 mg/100 g), niacin (7.9 mg/100 g), and folic acid (1.57 mg/100 g); and rich in minerals such as calcium (600 mg/100 g), iron (106.1 mg/100 g), and zinc (5.8 mg/100 g). The oral administration of AFE?+?VME in obese mice reduced body weight, tissue weight, adipocyte size, and lipid accumulation in the liver compared with HFD control mice. AFE?+?VME also decreased serum triglyceride, total cholesterol, and leptin concentrations. Furthermore, AFE?+?VME markedly increased the mRNA expression of peroxisome proliferator-activated receptor-? (PPAR-?), uncoupling protein-2 (UCP-2), and adiponectin and decreased leptin expression in the epididymal white adipose tissue. Our results suggest that the extract containing A. fistulosum and V. mandshurica improved lipid metabolism via the up-regulation of PPAR-?, UCP-2, and adiponectin expression and the down-regulation of leptin in HFD-induced obese mice.Therefore, the extract containing Allium fistulosum and Viola mandshurica may be a potentially effective therapy for obesity and its related metabolic disorders such as hyperlipidemia and insulin resistance.
Project description:Oxidative stresses intensify the progression of diabetes-related behavioural changes and testicular injuries. Graviola (Annona muricata), a small tree of the Annonaceae family, has been investigated for its protective effects against diabetic complications, oxidative stress, and neuropathies. This study was planned to investigate the effects of graviola on behavioural alterations and testicular oxidative status of streptozotocin (STZ; 65 mg/kg)-induced diabetic rats. Forty adult male Wistar rats were equally allocated into four groups: control (received normal saline 8 ml/kg orally once daily), diabetic (received normal saline orally once daily), graviola (GR; received 100 mg/kg/day; orally once daily), and diabetic with graviola (Diabetic+GR; received 100 mg/kg/day; once daily). Behavioural functions were assessed using standard behavioural paradigms. Also, oxidative statuses of testis were evaluated. Results of behavioural observations showed that diabetes induced depression-like behaviours, reduction of exploratory and locomotor activities, decreased memory performance, and increased stress-linked behaviours. These variations in diabetic rats were happened due to oxidative stress. Interestingly, treatment of diabetic rats with graviola for four weeks alleviated all behavioural changes due to diabetes. Also, rats in graviola-treated groups had greater testicular testosterone and estradiol levels compared with diabetic rats due to significant rise in testicular acetyl-CoA acetyltransferase 2 expression. In the same context, graviola enhanced the antioxidant status of testicular tissues by significantly restoring the testicular glutathione and total superoxide dismutase that fell during diabetes. In addition, Graviola significantly decreased the expression of apoptotic (Bax) and inflammatory (interleukin-1?) testicular genes. In conclusion, these data propose that both the hypoglycemic and antioxidative potential of graviola are possible mechanisms that improve behavioural alterations and protect testis in diabetic animals. Concomitantly, further clinical studies in human are required to validate the current study.
Project description:The Kampo medicine bofutsushosan (BTS; Pulvis ledebouriellae compositae; Fang Feng Tong Sheng San) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet.Male ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0-2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment.Bofutsushosan (1.5-2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days' treatment. Twenty-five days' treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days' administration.In the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.
Project description:Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77.5 or 155 mg/kg/day for 8 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The gene expressions were analyzed using RT-qPCR and western blotting. Results: GTE modulated HED-induced body weight, fat accumulation, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein, free fatty acids, aspartate aminotransferase, and alanine aminotransferase. Moreover, GTE enhanced the serum high-density lipoprotein. Most importantly, the biomarkers of beige adipose tissue were up-regulated in WAT in GTE-given groups. GTE induced genes involved in different pathways of browning, and reduced transducin-like enhancer protein-3 in WAT. Conclusion: Our results suggest that GTE may improve obesity through inducing browning in HED-fed rats. Abbreviations: ALT: Alanine transaminase; AST: Aspartate transaminase; BAT: Brown adipose tissue; BMP-7: Bone morphogenetic protein-7; BW: Body weight; CIDEA: Cell death activator; CPT-1: Carnitine palmitoyltransferase-1; EFP: Epididymal fat pad; FFA: Free fatty acid; FGF-21: Fibroblast growth factor-21; GTE: Green tea extract; HDL: High-density lipoprotein; HED: high-energy diet; LDL: Low-density lipoprotein; MFP: Mesenteric fat pad; PGC-1?: Activates PPAR-? coactivator-1; PPAR-?: Peroxisome proliferator-activated receptor-?; PRDM-16: PR domain containing 16; RFP: Renal fat pad; SD: Sprague Dawley; TC: Total cholesterol; TG: Triacylglycerol; TLE-3: Transducin-like enhancer protein-3: UCP-1: Uncoupling protein-1; WAT: White adipose tissue.
Project description:Diabetes mellitus has been a menace to mankind from time immemorial. However, a natural product such as <i>U. chamae</i> P. Beauv (Annonaceae) offers alternative treatment for diabetes mellitus. The study aimed at evaluating antidiabetic activity of the ethanolic root extract of <i>U. chamae</i> in alloxan-induced diabetic rats. Diabetes was induced in Sprague Dawley rats after overnight fast with 150?mg/kg alloxan intraperitoneally. After 72?h, those with plasma glucose levels >200?mg/dl were classified as diabetic. Five diabetic rats in each group were treated daily for 14?days orally with 100, 250, and 400?mg/kg of the extract, glibenclamide (71?<i>µ</i>g/kg) and pioglitazone (429?<i>µ</i>g/kg), respectively, while another group was untreated. Control received 0.5?ml of <i>Acacia senegal</i>. Effects of extract on glucose, other biochemical, and hematological parameters were evaluated. <i>?</i>-amylase and <i>?</i>-glucosidase inhibitory activities of extract and its fractions were also evaluated. Percentage inhibition and IC<sub>50</sub> values were determined. Diabetic control was achieved on the 7th day of the study with 100, 250, and 400?mg/kg of the extract showing glucose reduction of 72.14%, 78.75%, and 87.71%, respectively. The HDL-cholesterol levels of diabetic rats treated with extracts were significantly increased. Extract and its fractions caused <i>?</i>-amylase and <i>?</i>-glucosidase inhibition. Histologically, pancreas of diabetic rats treated with extract showed regenerated islet cells which were not seen in rats treated with glibenclamide and pioglitazone. This study showed that <i>U. chamae</i> has antidiabetic activity which may be through <i>?</i>-amylase and <i>?</i>-glucosidase inhibition and regeneration of pancreatic beta cells. Also, it may reduce the risk of cardiovascular disease by increasing HDL-cholesterol levels.
Project description:BACKGROUND:Diabetes and its related complications remain to be a major clinical problem. We aim to investigate the antidiabetic mechanistic actions of Plicosepalus Acaciae (PA) flowers in streptozotocin (STZ)-induced diabetic rats. METHODS:After diabetes induction, rats were divided randomly into five groups, including: 1) normal control group, 2) diabetic control group, 3) diabetic group treated with 150?mg/kg of ethanolic extract of PA flowers, 4) diabetic group treated with 300?mg/kg of ethanolic extract of PA flowers, and 5) diabetic group treated with 150?mg/kg of metformin. After 15?days of treatment; fasting blood glucose, glycated hemoglobin (HBA1c%), insulin, C-peptide, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), triglyceride (TGs), total cholesterol (Tc), low density lipoprotein cholesterol (LDL-c), very LDL (VLDL), high DLc (HDL-c), tumor necrosis factor-? (TNF-?), and interleukin-6 (IL-6) levels were assessed. Histopathology of pancreas was also assessed. RESULTS:The results showed that PA flower ethanolic extract significantly reduced blood glucose, HBA1c%, MDA, TGs, Tc, VLDL, LDL-c, TNF-?, and IL-6 levels in a dose-dependent manner. All these parameters were already increased by diabetic induction in the untreated diabetic group. Treatment of diabetic rats with PA flower increased insulin, HDL-c, GSH, catalase, and SOD levels. Histological examination showed that the PA flower caused reconstruction, repair, and recovery of damaged pancreas when compared with the untreated group. CONCLUSIONS:PA flower has a potential role in the management of diabetes as complementary and alternative therapy, due to its antioxidant, anti-inflammatory, hypolipidemic, hypoglycemic and insulin secretagogue effects.